73 articles - From Friday Nov 04 2022 to Friday Nov 11 2022
Guidelines and related publications, position statements, white papers, technical reviews, consensus statements, etc…
meta-analyses and systematic reviews
| Lancet Haematol |
Second primary malignancies in patients with haematological cancers treated with lenalidomide: a systematic review and meta-analysis. Further investigations are needed to improve understanding on why lenalidomide only promotes SPM in patients with multiple myeloma. Funding None. |
| Thromb Haemost |
Mortality of Escalation and Modulation Antithrombotic Therapy in Coronary Artery Disease Patients: A Meta-analysis of Randomized Controlled Trials. Either escalation or modulation of ATT has little benefit in all-cause mortality. The variability of the treatment effects on all-cause mortality was mainly attributed to the variability of major or minor bleeding, but not to MI. |
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
Predictors of anemia response to momelotinib therapy in myelofibrosis and impact on survival. This survival advantage was also noted in transfusion-dependent patients (3.7 vs 1.9 |
| Blood |
EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy. A large proportion of post-ALL lymphoid neoplasms are associated with an immunodeficient state, likely precipitated by ALL maintenance therapy. Awareness of this underrecognized entity and pertinent diagnostic tests are crucial for early diagnosis and optimal therapy. |
Genetic basis and molecular profiling in myeloproliferative neoplasms. Factors that control the conversion from clonal hematopoiesis to MPN include inherited predisposition, presence of additional mutations and inflammation. The complete knowledge of the mutational landscape in individual MPN patients is now increasingly being used to predict outcome and chose the optimal therapy. |
How I treat thrombotic microangiopathy in the era of rapid genomics. By taking precedence over a phenotypic approach, an unbiased genomic-focused analysis maximizes the chances of discovering new descriptions related to a given variant. Presented here are four cases of TMA which highlight these issues and substantiate the promise of fast-track genomic sequencing. |
Impact of poverty and neighborhood opportunity on outcomes for children treated with CD19-directed CAR T-cell therapy. Investigation of multicenter outcomes and access disparities outside of clinical-trial settings is warranted. Clinical trials: NCT01626495; NCT02435849 ; NCT02374333; NCT02228096; NCT02906371. |
Lentiviral Gene Therapy for X-Linked Chronic Granulomatous Disease Recapitulates Endogenous CYBB Regulation and Expression. cepacia infection, and restored healthy donor levels of anti-microbial oxidase activity in neutrophils derived from X-CGD patient HSPCs. Our findings validate the bioinformatics-guided design approach and have yielded a novel lentiviral vector with clinical promise for the treatment of X-CGD. |
Liver sinusoidal endothelial cells induce BMP6 expression in response to non-transferrin bound iron. Our data suggest that during systemic iron overload, LSECs internalize NTBI, which promotes oxidative stress and thereby transcriptionally induces Bmp6 via Nrf2. Tfr1 appears to contribute to iron sensing by LSECs mostly under low iron conditions. |
Natural killer T cells and other innate-like T lymphocytes as emerging platforms for allogeneic cancer cell therapy. Both unmodified NKTs, which specifically recognize CD1d-bound glycolipid antigens expressed by some types of tumors, and CAR-redirected NKTs are in development as the next generation of allogeneic cell therapy products. In this review, we describe studies on the biology of NKTs and other types of innate-like T cells and summarize experiences in the clinic with unmodified and CAR-redirected NKTs, including recent interim reports on allogeneic NKTs. |
Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homeostasis. Fitness loss and associated RNA transcriptome and splicing alterations in RXRa; RXRb-deficient HSCs are prevented by Myc haploinsufficiency. Our study reveals the critical importance of RXRs for the maintenance of HSC fitness and their protection from premature aging. |
| Blood Adv |
Applying CRISPR-Cas9 screens to dissect hematological malignancies. Specifically, within blood cancers, current CRISPR screens have specifically focused on improving our understanding of drug resistance strategies, disease biology, development of novel therapeutic approaches, and identifying the molecular mechanisms of current therapies, with an underlying aim of improving disease outcomes. Here, we review the development of CRISPR-Cas9 genome editing strategy, explicitly focusing on the recent advances in the CRISPR-Cas9 based screening approaches, its current capabilities, limitations, and future applications in the context of hematological malignancies. |
Cost-Effectiveness of Chimeric Antigen Receptor T-Cell Therapy in Adults with Relapsed or Refractory Follicular Lymphoma. Under current pricing, CAR-T is unlikely to be cost-effective in unselected FL patients in the third-line setting. Both randomized clinical trials and longer-term clinical follow up can help clarify the benefits of CAR-T and optimal sequencing in patients with FL. |
Creating an Automated Contemporaneous Cohort in Sickle Cell Anemia to Predict Survival After Disease-Modifying Therapy. Compared to those receiving no disease-modifying treatment, those treated with hydroxyurea therapy had significantly lower hazard of mortality (hazard ratio=0.38, p=0.016), but no statistical difference for those receiving regular blood transfusions compared to no disease-modifying therapy (hazard ratio=0.71, p=0.440). An automated contemporaneous SCA cohort can be generated to estimate mortality in children and adults with SCA. |
Downregulated KLF2 in polycythemia vera and essential thrombocythemia induces prothrombotic gene expression. In PV and ET patients, KLF2 expression was induced by pegylated interferon-a (PegINFa) but not by hydroxyurea treatments. These data suggest that KLF2 may be a regulator of PV and ET thrombosis and a novel therapeutic target to prevent thrombosis. |
Gata1s mutant mice display persistent defects in the erythroid lineage. Here we demonstrate that Gata1s mutant mice display macrocytic anemia and features of aberrant megakaryopoiesis throughout life, culminating in profound splenomegaly and bone marrow fibrosis. These data support the use of this animal model for studies of GATA1 deficiencies. |
Hypodiploidy has Unfavorable Impact on Survival in Pediatric Acute Myeloid Leukemia:An I-BFM Study Group collaboration. Allogeneic stem cell transplantation (SCT) in first complete remission (CR1) (n=18) did not mitigate the unfavorable outcome of hypodiploidy (adjusted HR for OS was 1.5, p=0.42). We identified pediatric hypodiploid AML as a rare subgroup with an inferior prognosis even in patients treated with SCT in CR1. |
Low toxicity and excellent outcomes in patients with DLBCL without residual lymphoma at the time of CD19 CAR T-cell therapy. Our findings suggest that, in patients with R/R DLBCL who have an indication for CAR T-cell therapy, treating patients in complete remission at time of infusion is feasible, safe, and associated with favorable disease control. Further exploration in a larger clinical trial setting is warranted. |
Pharmacokinetics, pharmacodynamics, safety and efficacy of crizanlizumab in patients with sickle cell disease. Results here demonstrate the PK/PD properties of crizanlizumab in SCD patients, and the potential sustained efficacy and long-term safety of the drug after >12 months' treatment. This trial is registered at as NCT03264989. |
Prospective changes of pancreatic iron in patients with thalassemia major and association with chelation therapy. The reduction in pancreatic iron levels was comparable among the three groups. Our data showed that it is difficult to remove the iron from the pancreas and that the three iron chelators in monotherapy have a comparable efficacy. |
Reg3a levels at day of allogeneic stem cell transplantation predict outcome and correlate with early antibiotic use. Reg3a, a known biomarker of acute GI GvHD correlates with intestinal dysbiosis induced by early antibiotic treatment in the period of pretransplant conditioning. Serum concentrations of Reg3a measured on the day of graft infusion are predictive of the risk for TRM of allogenic SCT recipients. |
The promising efficacy of a risk-based letermovir use strategy in CMV-positive allogeneic hematopoietic cell recipients. In both risk groups, the two periods were comparable for CMV disease, overall survival, progression-free survival, relapse, and non-relapse mortality. We concluded that a risk-based strategy for letermovir use is an effective strategy which maintains the high efficacy of letermovir in high-risk patients but allows some low-risk patients not to use letermovir. |
Waldenström Macroglobulinemia Whole Genome Reveals Prolonged Germinal Center Activity and Late Copy Number Aberrations. In summary, WGS analysis in WM allows the demonstration of sustained germinal center activity over time and allows the reconstruction of the temporal evolution of specific genomic features. In addition, our data suggests that, while MYD88-mutations are central to WM clone establishment and can be observed in precursor disease, CNA may contribute to later phases, and may be used as a biomarker for progression risk from precursor conditions to symptomatic disease. |
| Blood Cancer J |
GATA-3 is a proto-oncogene in T-cell lymphoproliferative neoplasms. The discovery that p300-dependent acetylation regulates GATA-3 mediated transcription by attenuating DNA binding has novel therapeutic implications. As most patients afflicted with GATA-3 driven T-cell neoplasms will succumb to their disease within a few years of diagnosis, these findings suggest opportunities to improve outcomes for these patients. |
The PIP4K2 inhibitor THZ-P1-2 exhibits antileukemia activity by disruption of mitochondrial homeostasis and autophagy. The minimal effects of THZ-P1-2 observed in healthy CD34 + cells suggest a favorable therapeutic window. Our study provides insights into the pharmacological inhibition of PIP4K2s targeting mitochondrial homeostasis and autophagy, shedding light on a new class of drugs for acute leukemia. |
| J Hematol Oncol |
JMJD4-demethylated RIG-I prevents hepatic steatosis and carcinogenesis. Decreased RIG-I in HcPCs promotes necroinflammation-induced hepatocarcinogenesis, while increased constitutive methylated RIG-I enhances steatosis and NASH-induced hepatocarcinogenesis. JMJD4-demethylated RIG-I prevents both necroinflammation and NASH-induced hepatocarcinogenesis, which provides mechanistic insight and potential target for preventing HCC. |
Safe and effective off-the-shelf immunotherapy based on CAR.CD123-NK cells for the treatment of acute myeloid leukaemia. Our data indicate the feasibility of an innovative off-the-shelf therapeutic strategy based on CAR.CD123-NK cells, characterized by remarkable efficacy and an improved safety profile compared to CAR.CD123-T cells. These findings open a novel intriguing scenario not only for the treatment of refractory/resistant AML patients but also to further investigate the use of CAR-NK cells in other cancers characterized by highly difficult targeting with the most conventional T effector cells. |
| Lancet Haematol |
Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone as induction therapy for newly diagnosed, transplantation-eligible patients with multiple myeloma (GMMG-HD7): part 1 of an open-label, multicentre, randomised, active-controlled, phase 3 trial. Interpretation Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone for induction therapy improved rates of MRD negativity with no new safety signals in patients with newly diagnosed transplantation-eligible multiple myeloma. Funding Sanofi and Bristol Myers Squibb (Celgene). |
| Leukemia |
Genetic deletion and pharmacologic inhibition of E3 ubiquitin ligase HOIP impairs the propagation of myeloid leukemia. Finally, the administration of thiolutin, which inhibits the catalytic activity of Hoip, improved the survival of recipients in murine myeloid leukemia and suppressed propagation in the patient-derived xenograft model of myeloid leukemia. Collectively, these data indicate that inhibition of LUBAC activity may be a valid therapeutic target for myeloid leukemia. |
Identification and interrogation of the gene regulatory network of CEBPA-double mutant acute myeloid leukemia. We identify the binding sites of mutated C/EBPa proteins in primary cells, we show that C/EBPa, AP-1 factors and RUNX1 colocalize and are required for AML maintenance, and we employ single cell experiments to link important network nodes to the specific differentiation trajectory from leukemic stem to blast cells. Taken together, our study provides an important resource which predicts the specific therapeutic vulnerabilities of this AML subtype in human cells. |
In vivo PDX CRISPR/Cas9 screens reveal mutual therapeutic targets to overcome heterogeneous acquired chemo-resistance. Accordingly, venetoclax re-sensitized derivative tumors towards chemotherapy, despite genomic heterogeneity, demonstrating direct translatability of the approach. Hence, despite the presence of multiple resistance-associated genomic alterations, effective rescue treatment for polychemotherapy-resistant tumors can be identified using functional testing in preclinical models. |
Inhibition of USP1 reverses the chemotherapy resistance through destabilization of MAX in the relapsed/refractory B-cell lymphoma. Moreover, pimozide showed a synergetic effect with etoposide, a chemotherapy drug, in cell and mouse models of rituximab/chemotherapy resistant DLBCL. Our study highlights the critical role of USP1 in the rituximab/chemotherapy resistance of DLBCL through deubiquitylating MAX, and provides a novel therapeutic strategy for rituximab/chemotherapy resistant DLBCL. |
Loss of bisecting GlcNAcylation on MCAM of bone marrow stoma determined pro-tumoral niche in MDS/AML. MCAM on stromal cell surface with reduced bisecting GlcNAc bound strongly to CD13 on myeloid cells, activated responding ERK signaling, and thereby promoted myeloid cell growth. Our findings, taken together, suggest a novel mechanism whereby MDS/AML clonal cells generate a self-permissive niche by modifying glycosylation level of stromal cells. |
mTOR inhibition amplifies the anti-lymphoma effect of PI3Kß/d blockage in diffuse large B-cell lymphoma. Collectively, our study reveals that subsets of DLBCLs are addicted to PI3Kß/d signaling and thus identifies a previously unappreciated role of the PI3Kß isoform in DLBCL survival. Furthermore, our data demonstrate that combined targeting of PI3Kß/d and mTOR is effective in al major DLBCL subtypes supporting the evaluation of this strategy in a clinical trial setting. |
Outcomes of first therapy after CD19-CAR-T treatment failure in large B-cell lymphoma. The presence of =2 of these factors was associated with inferior OS compared to =1 (56% vs 19%). In this largest analysis to date of patients who progressed or relapsed after CD19-CAR-T, survival is poor, though novel agents such as polatuzumab and lenalidomide may have hold promise. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Ann Oncol |
COP27 Climate Change Conference: urgent action needed for Africa and the world. It is highly unjust that the most impacted nations have contributed the least to global cumulative emissions, which are driving the climate crisis and its increasingly severe effects. North America and Europe have contributed 62% of carbon dioxide emissions since the Industrial Revolution, whereas Africa has contributed only 3% (14). |
| Blood |
| CA Cancer J Clin |
Cancer statistics for American Indian and Alaska Native individuals, 2022: Including increasing disparities in early onset colorectal cancer. These findings highlight the need for more effective strategies to reduce the prevalence of chronic oncogenic infections and improve access to high-quality cancer screening and treatment for AIAN individuals. Mitigating the disparate burden will require expanded financial support of tribal health care as well as increased collaboration and engagement with this marginalized population. |
| J Hematol Oncol |
Natural killer cells in clinical development as non-engineered, engineered, and combination therapies. Additionally, the competitive landscape and business field is presented. This review offers a comprehensive overview of the effort driven by biotech and pharmaceutical companies and by academic centers to bring NK cell therapies to pivotal clinical trial stages and to market authorization. |
| Lancet Haematol |
misc publications eg case reports, tools of the trade, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| CA Cancer J Clin |
| Lancet Haematol |
| Leukemia |
| Thromb Haemost |
Letters to the editors and authors’ replies
| Am J Hematol |
| Blood Cancer J |
| J Hematol Oncol |
FIT-based risk-stratification model effectively screens colorectal neoplasia and early-onset colorectal cancer in Chinese population: a nationwide multicenter prospective study. The risk-stratification model identified 73.5% CN, 82.6% ACN, and 93.6% CRC when guiding 52.7% individuals to receive colonoscopy and identified 55.8% early-onset ACNs and 72.7% early-onset CRCs with only 25.6% young individuals receiving colonoscopy. The risk-stratification model showed a good risk-stratification ability for CN and early-onset CRCs in Chinese population, including individuals with NSGS and young age. |
| Leukemia |